Hypoxia-inducible factors and hypertension: lessons from sleep apnea syndrome.

Hypoxia-inducible factors and hypertension: lessons from sleep apnea syndrome.
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DOI:
10.1007/s00109-015-1274-2
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发表时间:
2015-05
影响因子:
4.7
通讯作者:
Prabhakar, Nanduri R.
Prabhakar, Nanduri R.
中科院分区:
医学2区
文献类型:
--
作者:
Nanduri, Jayasri;Peng, Ying-Jie;Yuan, Guoxiang;Kumar, Ganesh K.;Prabhakar, Nanduri R.

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系统性高血压是最常见的心血管疾病之一。睡眠呼吸障碍(SDB)伴有反复呼吸暂停是发生原发性高血压的主要危险因素。慢性间歇性缺氧(CIH)是反复呼吸暂停的标志性表现。根据 SDB 患者的 O2 曲线建立的啮齿动物模型表明,CIH 是引起全身性高血压的主要刺激因素。本文综述了 CIH 诱发高血压的生理和分子基础。生理学研究发现,颈动脉体化学感应反射增强以及由此导致的交感神经活动增加是 CIH 诱发高血压的主要原因。分子机制分析表明,CIH 激活缺氧诱导因子 (HIF)-1 并抑制 HIF-2 介导的转录。 HIF-1 和 HIF-2 介导的转录失调会导致促氧化剂和抗氧化剂酶基因表达失衡,导致化学感应反射中活性物质 (ROS) 的产生增加,而化学感应反射是高血压发生的关键。
Systemic hypertension is one of the most prevalent cardiovascular diseases. Sleep disordered breathing (SDB) with recurrent apnea is a major risk factor for developing essential hypertension. Chronic intermittent hypoxia (CIH) is a hallmark manifestation of recurrent apnea. Rodent models patterned after the O2 profiles seen with SDB patients showed that CIH is the major stimulus for causing systemic hypertension. This article reviews the physiological and molecular basis of CIH-induced hypertension. Physiological studies have identified that augmented carotid body chemosensory reflex and the resulting increase in sympathetic nerve activity is a major contributor to CIH-induced hypertension. Analysis of molecular mechanisms revealed that CIH activates hypoxia-inducible factor (HIF)-1 and suppresses HIF-2- mediated transcription. Dysregulation of HIF-1- and HIF-2- mediated transcription leads to imbalance of pro-oxidant and anti-oxidant enzyme gene expression resulting in increased reactive species (ROS) generation in the chemosensory reflex which is central for developing hypertension.
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